Superficial fungal infections of skin, hair, nails, or mucous membranes, are still very common among all populations. In particular, onychomycosis is a fungal infection of the nails. The onychomycosis are frequent, involving up to about 15% of persons between the ages of 40 and 60 years. Some estimates suggest that onychomycosis affects about 6 to about 13% of the North American population, with an estimated 4.9 to 12.3 million people being affected in the United States. In European populations, the estimated overall prevalence of onychomycosis is in the range of about 3 to about 10%.
Delivery of antifungal agents through the nail into the nail bed and surrounding skin has been minimally effective for the treatment of onychomycosis (infections of the fingernails, toenails, and immediate adjacent surrounding skin) in the form of a nail lacquers, primarily because the film forming water-insoluble polymers used limit the diffusion of the drug from the dried film into the nail and skin, and because previous nail lacquer compositions do not contain the optimum balance of permeation enhancement to deliver the drug to both the nail and surrounding skin in an amount sufficient for optimal antifungal activity.
Fungal infection of the nails, commonly referred to as onychomycosis, is most frequently caused by dermatophytes, but can also be caused by molds and Candida sp. Onychomycosis is predominantly present in toenails rather than fingernails, in males, and in the elderly. Onychomycosis is most commonly caused by Trichophyton rubrum (T. rubrum), Trichophyton mentagrophytes (T. mentagrophytes), and Epidermophyton floccusum (E. floccusum). Onychomycosis due to nondermatophytes is usually caused by Candida species, such as Candida albicans, and is more likely to cause invasive nail disease in fingernails than in toenails of immunocompetent individuals.
Onychomycosis has medical significance especially in individuals having certain diseases, such as diabetes and others where the individual is immunocompromised. Also onychomycosis can have a substantial undesirable effect on daily living activities, such as ambulation, and spontaneous remission is rare. The current treatments of onychomycosis include oral administration of antifungal agents, such as itraconazole (distributed under the tradename, SPORONOX®, by Ortho Biotech Products L.P.), and terbinafine (distributed under the tradename, LAMISIL®, by Novartis Pharmaceuticals Corporation). While itraconazole and terbinafine hydrochloride offer significant cure rates, shorter treatment regimens and lower levels of adverse events compared to the imidazoles (e.g., ketoconazole), clinically significant drug interactions can occur and the therapeutic period requires at least a few months. Thus, there is an ongoing need and desire for a non-oral management of onychomycosis.
One attempt has been made employing the antifungal agent, ciclopirox distributed commercially under the trade name PENLAC™ Nail Lacquer by Dermik Laboratories, Inc.), as an 8% topical solution containing a water-insoluble, film-forming polymer, and is described in U.S. Pat. No. 4,957,730 to Bohn, et al. Another antifungal nail lacquer compositions utilizing a water-insoluble film forming polymer is described in U.S. Pat. No. 6,495,124 by Samour. Yet another nail lacquer formulation contains 5% amorolfine, a morpholine derivative, and is manufactured by Roche Laboratories under the trade name LOCERYL™. However, water-insoluble film-forming polymers, such as used in conventional nail lacquer compositions are fast drying (less than one minute) solution of water-insoluble polymers and, if brushed onto the skin area surrounding the nail, tend to irritate the skin area. Additionally, such traditional, water-insoluble, fast drying, film-forming polymers produce high viscosity nail lacquer compositions and thus limit the mobility and time for active exchange of the antifungal agent between the film and the nail plate resulting in loss of treatment efficacy. In some instances, the nail lacquers are suitable only for treatment of mild onychomycosis without nail matrix involvement, and systemic treatment is still required for severe onychomycosis involving the nail bed.
An attempt employing azole derivatives at 0.5-1% concentration applied from a composition containing water-insoluble fatty components, solubilizers and a quick drying, water-soluble, polyvinylpyrrolidone, or vinylacetate copolymers and terpolymers thereof, is described in Canadian Patent No. 1,175,355 and European Patent No. 055,397.
The present dual action antifungal topical nail coat compositions and methods provide a fungicidal regimen suitable for the treatment of onychomycosis of varying severities in mammals in need of such treatment.